A NEWLY discovered group of toxic proteins believed to trigger Alzheimer's disease might be an important step towards effective treatment for the disease, scientists said yesterday.
The proteins are thought to interfere with the brain signalling mechanisms necessary for learning and memory even before the brain damage associated with more advanced stages of the dementing disease.
This has given rise to the hope that if the symptoms were caught at early stages they might be reversible.
The proteins, called amyloid beta-derived diffusible ligands (or ADDLs), were identified by a joint team of neuroscientists in Illinois and Southern California, who describe ADDLs as a surprising new form of the amyloid beta protein.
This is already known to accumulate as enormous fibres in Alzheimer's-afflicted brains, and a long-standing hypothesis has been that these fibres attack nerve cells and cause Alz-heimer's dementia. The scientists now have found that ADDLs, which are minuscule clumps of amyloid beta only a tiny fraction of the size of a fibre, may be more relevant to the disease process.
Their experiments in laboratory specimens found that, even at highly dilute concentrations, ADDLs interfered with long-term potentiation, one of the nerve cell processes that is essential to learning and memory.
Professor William Klein, of Northwestern University, Illin-ois, who led the study, said: ''Our work suggests that corruption by ADDLs of such signalling may account for the loss of synaptic memory formation at the early stages of Alzheimer's disease and for the nerve cell death and profound dementia at end stages of the disease.''
This dysfunction occurred well in advance of the cellular degeneration considered by many researchers to be the cause of Alzheimer's disease, and which - when it did occur - was most evident in the hippocampus, the brain's ''storage bin'' for short-term memory.
ADDLs apparently form when certain inflammatory proteins are present in the brain. One such protein, clusterin (or Apo J), is elevated in the brains of patients with Alzheimer's disease. Two of Klein's colleagues, Grant Krafft and Caleb Finch, had already found that clusterin could make amyloid protein toxic but prevented formation of small fibre particles or fibrils.
Based on these results, the collaborative group subsequently found that a combination of amyloid and clusterin resulted in the formation of ADDLs.
Finch said: ''Dogma holds that fibrils cause Alzheimer's disease. But we have found that even without fibrils, there can be devastating consequences for nerve cells.''
The group then developed tests which showed that ADDLs activate a protein known as Fyn, a reaction that ultimately results in cell death. Neurons in the brains of people with Alzheimer's disease have been found to have elevated amounts of Fyn.
They found that the mechanism through which ADDLs exert their toxicity is blocked by removal of Fyn. Blocking ADDL binding sites also afforded brain cells protection against the toxic effects of ADDLs.
Krafft said: ''While it is generally believed that Alzheimer's disease symptoms are due to nerve cell death, we were able to block memory mechanisms without nerve cell death. The implications of this work are that, if Alzheimer's disease symptoms are caught at early stages, they potentially could be reversed.''
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